Fertility and Germline Stem Cell Maintenance under Different Diets Requires nhr-114/HNF4 in C. elegans
Fertility and Germline Stem Cell Maintenance under Different Diets Requires nhr-114/HNF4 in C. elegans
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DOI：
10.1016/j.cub.2013.02.034
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发表时间：
2013-04-08
期刊：
影响因子：
9.2
通讯作者：
Eckmann, Christian R.
中科院分区：
文献类型：
--
作者：
Gracida, Xicotencatl;Eckmann, Christian R.
由于自主过程和与肠道微生物的有益关系，动物可以在可变的食物资源中茁壮成长[1]。食物的摄入会引起主要的生理变化，而这些变化会被维持机体内稳态的短暂的系统反应所抵消。这种外部信息的整合是通过核受体等细胞感觉元素实现的，核受体对特定线索的反应调节基因表达[2]。鉴于生殖系干细胞(GSCs)对生殖系发育和物种延续的重要性，有理由认为GSCs可能不受环境扰动的负面影响。然而，据我们所知，目前还没有关于保护GSCs免受有害饮食代谢物影响的机制的报道。以秀丽隐杆线虫为模型，我们报道了保守的核受体NHR-114/HNF4的体细胞活性保护GSC免受食物代谢物的影响。在没有NHR-114和某些细菌饮食的情况下，否则在身体上正常的动物会在发育过程中积累生殖细胞分裂缺陷并变得不育。我们发现，在NHR-114(-)动物中，生殖系缺陷和不育的诱导取决于细菌相对于必需氨基酸色氨酸的代谢状态。这说明了一种动物-微生物的相互作用，在这种相互作用中，体细胞核受体活性通过缓冲饮食中的代谢物来保存生殖系，最有可能的是通过体细胞解毒反应。总体而言，我们的发现揭示了一种史无前例的、可能在进化上保守的体细胞到生殖系的沟通轴，它在不同的食物资源上保持着生殖的健壮性。
Animals can thrive on variable food resources as a result of autonomous processes and beneficial relationships with their gut microbes [1]. Food intake elicits major physiological changes, which are counteracted by transient systemic responses that maintain homeostasis in the organism. This integration of external information occurs through cellular sensory elements, such as nuclear receptors, which modulate gene expression in response to specific cues [2]. Given the importance of germline stem cells (GSCs) for the development of the germline and the continuity of species, it is reasonable to assume that GSCs might be shielded from the negative influence of environmental perturbations. To our knowledge, however, there are no mechanisms reported that protect GSCs from harmful dietary metabolites. Using Caenorhabditis elegans as a model, we report that the somatic activity of the conserved nuclear receptor nhr-114/HNF4 protects GSC integrity from dietary metabolites. In the absence of nhr-114 and on certain bacterial diets, otherwise somatically normal animals accumulate germ cell division defects during development and become sterile. We found that, in nhr-114(-) animals, the induction of germline defects and sterility depend on bacterial metabolic status, with respect to the essential amino acid tryptophan. This illustrates an animal-microbe interaction in which somatic nuclear receptor activity preserves the germline by buffering against dietary metabolites, most likely through a somatic detoxifying response. Overall, our findings uncover an unprecedented, and presumably evolutionarily conserved, soma-to-germline axis of communication that maintains reproductive robustness on variable food resources.